线粒体移植增强心肌损伤后巨噬细胞的修复能力。

IF 14.1 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Yuning Zhang, Xiaolei Sun, Yawei Jin, Kanghui Chen, Lu Zhang, Xiong Gao, Mohan Li, Ze Yuan, Jianguo Jia, Aijun Sun, Junbo Ge
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引用次数: 0

摘要

病理重塑的心肌缺血微环境,以持续缺氧、代谢不足和炎症介质积聚为特征,严重破坏线粒体稳态。这种功能障碍建立了一个自我延续的循环,损害了协调的愈合级联,损害了心肌梗死(MI)后的心脏组织修复。为了抵消这些影响,研究人员提出了一种线粒体增强的新策略,即将健康的外源线粒体引入巨噬细胞以产生线粒体移植的巨噬细胞(Mito-T-Macros或MTMs),这些巨噬细胞可以抵抗心肌梗死后应激。线粒体移植(MT)有效诱导巨噬细胞向修复性m2样表型极化,从而增强促愈合功能,包括迁移、侵袭和吞噬。在体内,MTM治疗通过减少纤维化、限制细胞凋亡和促进血管生成来增强心肌梗死后的心功能和减轻左心室重构。从机制上讲,MT加速巨噬细胞向修复状态的表型转变,并延长其在愈合阶段的活性。值得注意的是,一部分移植线粒体从mtm中释放出来,随后被心肌细胞内化,这表明心肌支持的另一种机制。总的来说,MT增强了巨噬细胞的修复能力,并有助于MTMs改善心肌梗死后心脏重构的治疗效果。这些发现支持MTM治疗作为一种有希望和创新的方法来修复心肌梗死后的心肌损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mitochondrial Transplantation Augments the Reparative Capacity of Macrophages Following Myocardial Injury.

The pathologically remodeled myocardial ischemic microenvironment, characterized by sustained hypoxia, metabolic insufficiency, and accumulation of inflammatory mediators, severely disrupts mitochondrial homeostasis. This dysfunction establishes a self-perpetuating cycle that impairs the coordinated healing cascade and compromises cardiac tissue repair following myocardial infarction (MI). To counteract these effects, a novel strategy of mitochondrial augmentation is proposed, whereby healthy exogenous mitochondria are introduced into macrophages to generate mitochondria-transplanted macrophages (Mito-T-Macros or MTMs), which can resist post-MI stress. Mitochondrial transplantation (MT) effectively induces macrophage polarization toward a reparative M2-like phenotype, thereby enhancing pro-healing functions, including migration, invasion, and phagocytosis. In vivo, MTM therapy enhances cardiac function after MI and attenuates left ventricular remodeling by reducing fibrosis, limiting apoptosis, and promoting angiogenesis. Mechanistically, MT accelerates the phenotypic transition of macrophages to a reparative state and prolongs their activity during the healing phase. Notably, a portion of the transplanted mitochondria are released from MTMs and subsequently internalized by cardiomyocytes, suggesting an additional mechanism of myocardial support. Overall, MT enhances the reparative capabilities of macrophages and contributes to the therapeutic efficacy of MTMs in ameliorating post-MI cardiac remodeling. These findings support MTM therapy as a promising and innovative approach for repairing myocardial injury following MI.

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来源期刊
Advanced Science
Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
18.90
自引率
2.60%
发文量
1602
审稿时长
1.9 months
期刊介绍: Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.
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